Background: Lupus Nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE) is one of the most serious and prevalent manifestations. The procedure of renal biopsy is harmful and accompanied by potential hazards. Therefore, introducing reliable biomarkers to predict LN is exceedingly worthwhile. In the current study, we compared the diagnostic values of circulating autoantibodies against dsDNA, C1q, C3b, SSA, SSB, and Sm alone or in combination to predict LN.Methods: This study evaluated abovementioned autoantibodies in 40 healthy controls (HCs) and 95 SLE patients with different kidney involvements, including absent (n = 40), inactive (n = 20), and active (n= 35) LN using EIA method.Result: The frequency and odds ratio of anti-dsDNA (71.4%, OR=4.2), anti-C1q (62.9%, OR= 5.1), and the simultaneous existence of anti-C1q and anti-dsDNA (51.4%, OR=6) antibodies were significantly higher in the active LN group compared with both inactive and absent LN groups. Moreover, the levels of anti-C1q and anti-dsDNA antibodies positively correlated with disease activity in patients with SLE. The prevalence of these autoantibodies was associated with the severity of LN biopsies. Conclusion: These data suggest that anti-C1q and anti-dsDNA antibodies and also the simultaneous presence of them may be valuable diagnostic biomarkers for LN prediction in patients with SLE.